Purpose: To evaluate the validity of the Gleason score after neoadjuvant hormonal treatment as predictor of diseasespecific mortality after radical prostatectomy. Patients and Methods: A total of 2,880 patients with a complete data set and a mean follow-up of 10.3 years were studied; 425 of them (15%) had a history of hormonal treatment prior to surgery. The cumulative incidence of deaths from prostate cancer was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study combined effects of the variables on prostate cancer-specific mortality. Results: A higher portion of specimens with a history of neoadjuvant hormonal treatment were assigned Gleason scores of 8–10 (28 vs. 17%, p < 0.0001). The mortality curves in the Gleason score strata <8 vs. 8–10 were at large congruent in patients with and without neoadjuvant hormonal treatment. In patients with neoadjuvant hormonal treatment, a Gleason score of 8–10 was an independent predictor of prostate cancer-specific mortality; the hazard ratio was, however, somewhat lower than in patients without neoadjuvant hormonal treatment. Conclusion: This study suggests that the prognostic value of the post-radical prostatectomy Gleason score is not meaningfully jeopardized by heterogeneous neoadjuvant hormonal treatment in a routine clinical setting.

Changes in cis- and trans-regulatory elements are among the prime sources of genetic and phenotypical variation at species level. The introduction of cis- and trans- regulatory variation has played important roles in driving diversity, phenotypical differentiation, and evolution of humans. Therefore, variation that occurs on cis- and trans- regulatory elements becomes imperative to better understanding of human genetic diversity and its evolution. In this research, around 3360 gene regulatory factors (GRF) from the human genome were catalogued. This catalog includes genes that code for proteins that perform gene regulatory activities such DNA-depending transcription, RNA polymerase II transcription cofactor and co-repressor activity, chromatin binding and remodeling, among other 218 regulatory functions. This GRF catalog allowed us to initially explore how some GRF genes have evolved in humans, archaic humans (Neandertal and Denisovan) and non-human primate species. We discussed the likely phenotypical and medical effects that evolutionary changes in GRF genes may have introduced into the human genome; for instance, traits associated to speech and language capabilities, genomic recombination hotspots, diseases, among others. By using genome-wide datasets, we additionally looked for GRFs likely to be candidates for positive selection in three human populations: Utah Residents with Northern and Western Ancestry (CEU), Han Chinese in Beijing (CHB), and Yoruba in Ibadan (YRI). As result, we produced a set of candidates that gathers genes that may have contributed in shaping the phenotypical diversity currently observed in these populations; for instance, by introducing regulatory diversity at population-specific level. We additionally identified six GRF classes enriched for genes located in regions that are likely candidates for positive selection at population specific level. We found that out of the 41 DNA-binding GRF classes classified so far, six groups exhibited enrichment for genes located on regions that may have been under positive selection: C2H2 zinc finger, KRAB-ZNF zinc finger, Homeo domain, Tryptophan cluster, Fork head/winged helix and, and High-mobility HMG domain. We additionally identified three KRAB-ZNF gene clusters, in the chromosomes one, three, and 16, for the Asian population that exhibit regions with extended haplotype homozygosity EHH (larger than 100 kb). This EHH suggests that these regions have undergone positive selection in CHB population. Finally, considering that a representative fraction of the phenotypic diversity observed between humans and its closely related species are likely explained by changes in cis-regulatory elements (CREs), we investigated putative binding sites for the transcription factor GABPa. Using ChIP-Seq data generated from a human cell line (HEK293T), 11,619 putative GABPa CREs were found, Out of which 224 are putative human-specific. To experimentally validate the transcriptional activity of these human-specific CREs, reporter gene essays and knock-down experiments were performed. Our results supported the functionality of these human-specific GABPa CREs and suggest that at least 1,215 genes are primary targets of GABPa. Finally, further analyses depict scenarios that put together transcriptional regulation by GABPa and the evolution of particular human traits; for instance, cognitive abilities, breast morphology, lipids and glucose metabolic pathways, among others.

Patients and methods: Malignant supratentorial glioma (anaplastic astrocytoma, oligoastrocytoma, oligodendroglioma and glioblastoma incl. gliosarcoma), age 16-70y, KPS 50-100. Postoperative randomization to chemotherapy with either BCNU (B) (80 mg/m2 x 3 every 6 weeks) alone or additional VM 26 (V) (50 mg/m2 x 3 every 6 weeks) starting concomitant with radiotherapy. Central histopathological review was required. Primary endpoints were survival time (ST) and progression free survival (PFS) . In addition confirmative analysis of prognostic factors and their interaction with therapy was performed. Results: Eligible: 501 of 522 randomized pts: 82% WHO grade IV gliomas, 18% grade III gliomas. 57% male, mean KPS 74, mean age 50.9 years. The high incidence of lung toxicity – with a cumulative risk of 19% during the first year - was alarming. Survival was not significantly different ( median 50.3 (B) versus 52.4 (V) (weeks), but an increase in long term survivors was observed (18 months: 29% B, 34% V, 5 years 5% B, 12% V) and PFS showed a significant difference with a median of 31.4 (B) versus 34.3 (V) weeks. Qualitative interaction between KPS and therapy (p < 0.01) was demonstrated: pts with a KPS ≥ 70 benefited from additional VM26, those with reduced KPS < 70 did better with BCNU-monotherapy. Conclusion: Adding VM26 to BCNU is effective in the chemotherapy of malignant gliomas. Because of the demonstrated interaction with therapy performance status, not tumor grade is the crucial factor to determine application and aggressiveness of chemotherapy. With risk adapted therapy a significant proportion of patients even with glioblastoma survive for years in good general condition. BCNU should be replaced by an equipotent alkylans to avoid the unacceptable high rate of lung toxicity.

Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly. Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Genome-wide association studies (GWAs) have identified almost one hundred genetic loci associated with variances in human blood lipid phenotypes including very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol and triglycerides. Nevertheless the revealed loci only explain a small fraction of heritability and therefore a subtile phenotype of cholesterol homoestasis was examined in our study for the very first time. Methods and Results: Using a multi-stage approach of a GWA, firstly, a genome-wide analysis (Affymetrix 500K GeneChip) for serum lanosterol and serum total cholesterol using LC-MS/MS was conducted in 1495 participants of the KORA-S3/F3 cohort with subsequent replication in two additional independent samples of the the KORA-S3/F3 cohort (n = 1157) and CARLA cohort (n = 1760). Two genetic variants, SNP rs7703051 and rs17562686, in the HMGCR locus were significantly associated with serum lanosterol and showed similar effects of elevated serum lanosterol for each minor allele (combined n = 4412: p = 1,4 x 10-10, +7,1% and p = 4,3 x 10-6, +7,8%). Furthermore, rs7703051 showed a nominal statistical significance to serum cholesterol (p = 0,04). A combined analysis of both SNPs demonstrated that observed associations of rs17562686 can be partly explained by LD with rs7703051 being the primary polymorphism in that study. Nevertheless, rs17562686 shows consistent independent effects on serum lanosterol, thus being associated to a lipid phenotype for the very first time. The following SNP-fine mapping of the HMGCR locus was carried out in the CARLA cohort with subsequent validation in the LE-Heart cohort (n = 1895). The recently published SNP rs3846662 being in tight LD with rs7703051 could be associated with variances of serum lanosterol in both cohorts and functional in vivo studies of gen expression using qRT-PCR assays demonstrated a highly significant association of higher expression of alternatively spliced HMGCR mRNA lacking exon 13 with homozygosity for the rs3846662 major allele in 51 human liver samples (p < 0,01) and 958 human PBMCs (p = 2,1 x 10-7). The overall HMGCR gen expression was not affected. Further investigation of in vivo HMG-CoA reductase enzyme activity in both human samples (n = 48 and n = 55) using anionic exchange column chromatography and scintillation counting of [3-14C]-HMG-CoA and [5-3H]-mevalonolacton did not show any significant results. In addition there was not any association in the LE-Heart cohort between these SNPs and the development of CAD. Finally, rs7703051 could be replicated for already published total cholesterol (combined n = 4412) and rs3846662 for LDL-cholesterol (LE-Heart n = 1895). Since fine mapping in CARLA showed several SNPs throughout the HMGCR locus being in LD with rs17562686 we performed a DNA sequencing of the extended 5´-HMGCR promotor region in six human liver samples. A unknown SNP was discovered in the promotor but could not be associated with any of the examined phenotypes mentioned above. The minor allele of SNP rs5909 situated next to the stop codon and being in high LD with rs17562686 was associated with elevated serum lanosterol and slightly reduced HMGCR gen expression, but further studies including the above mentioned as well as measurement of 3’-UTR transcript lengths using qRT-PCR assays did not produce significant results. Conclusion: The phenotype serum lanosterol could be associated with genetic polymorphisms (e.g. rs7703051) in the HMGCR locus. Therefore already published associations of HMGCR with total cholesterol and LDL-cholesterol can be explained by variances of cholesterol homeostasis. The SNP rs17562686 could be associated with a phenotype of human blood lipids for the very first time. Subsequent gen expression analyses demonstrated a highly significant association of rs3846662 with variant patterns of HMGCR alternative splicing. A significant effect of alternatively spliced protein on enzyme activity and a association of these SNPs with CAD could not be shown.

Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

Der Einsatz von digitalen Menschmodellen erlaubt neben einer frühzeitigen ergonomischen Analyse die Gestaltung von Arbeitsprozessen und stellt ein hilfreiches Werkzeug in der Produkt- und Prozessgestaltung dar. Im Rahmen dieses Beitrages soll auf ausgewählte Schwerpunkte der Entwicklung des digitalen Menschmodells „The Smart Virtual Worker“ eingegangen werden. Das Forschungsprojekt soll einen Beitrag zur Lösung, der mit dem demografischen Wandel der Gesellschaft einhergehenden Herausforderungen leisten. Die daraus resultierenden Forschungsschwerpunkte liegen insbesondere in der Einbeziehung von Alterungs- und psychischen Faktoren in die Bewegungsgenerierung des Menschmodells und der Modellierung von Umweltbedingungen. In Umsetzung des Projektes wurde ein erstes Arbeitsszenario erarbeitet, auf dessen Basis die vorgenannten Forschungsaufgaben interdisziplinär gelöst werden sollen.

Humane corneale Endothelzellen (HCEC) bilden einen Monolayer aus differenzierten Zellen an der posterioren Oberfläche der Cornea und sind essenziell für den Erhalt der cornealen Transparenz. HCEC zeigen nahezu keine proliferative Aktivität in vivo und nur eine begrenzte Proliferationsfähigkeit in vitro. Bei übermäßigem Zellverlust aufgrund von Traumata, Erkrankungen oder des Alters kann die Transparenz der Cornea irreversibel beeinträchtigt werden und die Transplantation einer Spenderhornhaut erforderlich sein, um die Hornhauttransparenz und damit die Sehfähigkeit wiederherzustellen. Dabei ist die weltweite Begrenzung der medizinischen Versorgung mit hochwertigen Spenderhornhäuten das derzeit größte Problem für die Therapie von Cornea-assoziierten Erkrankungen. Zellersatzstrategien mit in vitro kultivierten, quantitativ und qualitativ ausreichenden Spenderzellen sollen die weitestgehend ausgereizten logistischen Ansätze zur Verringerung des Spendermangels ergänzen. Die Entwicklung einer abschaltbaren bzw. transienten Methode zur in vitro- und in situ-Vervielfältigung primärer HCEC ohne Verlust ihrer typischen morphologischen Merkmale würde die Herstellung sowie eine detaillierte und umfassende Charakterisierung von Transplantaten aus primären HCEC ermöglichen. In dieser Arbeit sollten daher zunächst verschiedene proliferationsfördernde Faktoren (PF) identifiziert werden, die nach stabilem retroviralen Gentransfer mit Integrations-kompetenten lentiviralen Vektoren (ICLV) in primären HCEC ein starkes proliferationsförderndes Signal provozieren, das eine Immortalisierung der Zellen zur Folge hat. Dabei sollte die Pseudotypisierung der ICLV-Partikel mit alternativen viralen Glykoproteinen zytopathische Effekte verringern und die Transduktionseffizienz steigern. Nachfolgend sollten die identifizierten PF auf ihre Fähigkeit, die Proliferation primärer HCEC transient zu stimulieren, ohne die Zellen dabei zu transformieren, getestet werden. Mit Hilfe verschiedener retroviraler Expressionssysteme sollte ein klinisch anwendbares System entwickelt werden, das eine kontrollierte, zeitlich begrenzte Stimulierung der Proliferation bei gleichzeitiger Unterdrückung eines tumorartigen Zellwachstums ermöglichte. Hierzu dienten 1) Integrase-defiziente lentivirale Vektoren (IDLV), die eine transiente Transgenexpression durch direkte Transkription des episomalen DNA-Vektorgenoms erlauben, und 2) das transiente Foamyvirus-Vektorsystem (TraFo-VS), dass auf der Enkapsidierung und dem Transfer nicht-viraler mRNA in permissiven Zielzellen basiert. Es konnte gezeigt werden, dass ICLV-Pseudotypen, die entweder eine SFVmcy-Glykoproteinvariante (ICLVSFV) oder das VSV-G-Protein enthielten (ICLVVSV), eine signifikante Transduktionseffizienz aufwiesen und dabei keine zytopathischen Effekte in den Zielzellen auslösten, weshalb beide Glykoproteine für weiterführende Experiment genutzt wurden. Unter Verwendung des optimierten ICLV-Systems konnten drei PF identifiziert werden, die eine reproduzierbare Immortalisierung primärer HCEC infolge stabiler Expression durch Transduktion mit den ICLV-Pseudotypen ermöglichten. Dazu zählten der Cyclin D1/CDK4-Proteinkomplex (4D), die SV40 T-Antigene (SV40T) sowie die transformierenden Proteine E6 und E7 (E6/E7) des HPV-16. Es konnte auch gezeigt werden, dass die Proliferation transduzierter primärer HCEC nach stabiler Transduktion mit PF-codierenden ICLV-Partikeln in einer dosisabhängigen Weise signifikant erhöht werden konnte. Untersuchungen mit IDLV-Varianten haben jedoch gezeigt, dass transduzierte HCEC ein vergleichbares proliferatives Verhalten wie ihre stabil transduzierten Äquivalente aufwiesen. Dies demonstrierte die restliche, geringgradige, nicht-kanonische Integrationskapazität von IDLV-Partikeln besonders im Zusammenhang mit der Expression von potenten PF. Nach erfolgter Transduktion mit TraFo-VP konnten die transferierten PF-codierenden mRNA in den Primärzellen nachgewiesen werden. Die Anwendung dieses Systems resultierte jedoch weder in einer nachweisbaren PF-Expression noch konnte eine proliferationsfördernde Wirkung in transduzierten Zellen festgestellt werden. Auch durch sequenzielle Transduktion der Zielzellen konnte keine Steigerung der Proliferationsrate induziert werden. Durch Verwendung von 50 fach konzentrierten SV40T-codierenden TraFo-VP konnte der mRNA-Transfer erhöht werden, wodurch dann auch die SV40T-Proteinexpression in den transduzierten Zellen nachweisbar wurde. Zudem konnte erstmalig gezeigt werden, dass sich im zeitlichen Verlauf sowohl die zellassoziierte SV40T-mRNA als auch die SV40T-Proteinkonzentration verringerte, bis sie nicht mehr nachweisbar war. Dabei konnte jedoch auch mit den konzentrierten TraFo VP keine nachweisbare transiente Immortalisierung primärer HCEC erreicht werden. Zusammenfassend kann festgestellt werden, dass eine permanente genetische Manipulation mit den viralen PF und dem 4D-Komplex eine Verlängerung der replikativen Lebensdauer ermöglichte und damit einhergehend die Immortalisierung primärer HCEC. Obgleich eine transiente Immortalisierung primärer HCEC mit den getesteten Systemen in dieser Arbeit nicht möglich war, ist eine klinische Anwendung des TraFo-VS, nicht aber des IDLV-Systems, in der angewandten Form, vielversprechend, um die Verfügbarkeit von qualitativ geeignetem Spendergewebe für die Transplantation bzw. Zellen für das Bioengineering des Hornhautendothels zu erhöhen. Daneben könnte das TraFo-VS ebenfalls genutzt werden, um andere zelluläre Funktionen in HCEC oder auch anderen Zielzellen transient zu modifizieren, z. B. Ionenfluss, replikative Seneszenz, Phagozytose oder Apoptose. / Human corneal endothelial cells (HCEC) form a monolayer of differentiated cells on the posterior surface of the cornea and are essential for maintaining corneal transparency. HCECs show almost no proliferative activity in vivo and only limited proliferative capacity in vitro. With excessive cell loss due to trauma, disease, or age-related degeneration, corneal transparency may be irreversibly compromised, and donor cornea transplantation may be required to restore vision. In this context, the global limitations in the medical supply of high-quality donor corneas are currently the most significant obstacle to the treatment of cornea-associated diseases. Cell replacement strategies using in vitro cultured donor cells of sufficient quantity and quality could complement the largely exhausted logistic approaches to alleviate donor shortage. The development of a method for strictly transient in vitro and in situ replication of primary HCECs without loss of their natural morphological characteristics would allow the production of well-characterized grafts derived from primary HCECs. To this end, I first aimed to identify different proliferation factors (PF) that provoke a robust proliferation-promoting signal in primary HCECs through stable retroviral gene transfer of candidate PF genes with integration-competent lentiviral vectors (ICLVs). Additionally, the pseudotyping of ICLV particles with alternative viral glycoproteins should reduce cytopathic effects and increase transduction efficiency. Subsequently, it should be clarified to what extent the identified PFs are capable of stimulating the proliferation of primary HCEC for a limited duration in a non-transformed context. Using different retroviral expression systems, I attempted to develop a clinically applicable system that allowed controlled, time-limited stimulation of proliferation while circumventing tumor-like cell growth. For this purpose, 1) integrase-deficient lentiviral vectors (IDLV), which allow transient transgene expression by direct transcription of the episomal DNA vector genome, and 2) the transient foamy virus vector system (TraFo-VS), which is based on encapsidation and transfer of non-viral mRNA in permissive target cells, were used. It was shown that ICLV pseudotypes containing either an SFVmcy glycoprotein variant (ICLVSFV) or the VSV-G protein (ICLVVSV) exhibited significant transduction efficiency without eliciting cytotoxic effects in target cells, highlighting both as viable candidates. Employing the optimized ICLV system, three PFs were identified that enabled reproducible immortalization of primary HCECs through stable expression after transduction with the ICLV pseudotypes. These included the cyclin D1/CDK4 protein complex (4D), the SV40 T antigens (SV40T), and the transforming proteins E6 and E7 (E6/E7) of HPV16. It was also shown that proliferation of transduced primary HCEC could be significantly increased in a dose-dependent manner following stable transduction with PF encoding ICLV particles. However, studies conducted using IDLV variants showed that PF-transduced HCEC exhibited a comparable proliferative behavior to their stably transduced equivalents. This demonstrated the residual, non-canonical integration capacity of IDLV particles especially in the context of potent PF expression. After successful transduction with TraFo-VP, the transferred PF-encoding mRNA could be detected in primary cells. However, application of this system did not result in detectable PF protein expression, nor could a proliferation-promoting phenotype be detected in transduced cells. Sequential transduction of target cells also failed to induce an increased proliferation rate. By using 50-fold concentrated SV40T-encoding TraFo-VPs, mRNA transfer could be increased, enabling detectable SV40T protein expression in transduced cells. In addition, it was shown for the first time that both cell-associated SV40T mRNA and SV40T protein levels decreased over time until they were no longer detectable. No observable transient immortalization of primary HCEC could be achieved even with the concentrated SV40T-encoding TraFo-VP. In conclusion, permanent genetic manipulation with the viral PFs and 4D protein complex allowed the prolonging of the cellular replicative lifespan in vitro and concomitant immortalization of primary HCEC. Although transient immortalization of primary HCECs was not possible with the systems tested in this investigation, clinical application of the TraFo-VS, but not the IDLV system as applied, remains a promising approach to increase the availability of suitable donor tissue for transplantation or cells for corneal endothelial bioengineering. Additionally, the TraFo-VS could also be used to transiently modify other cellular functions in HCEC or other target cells, e.g., ion flux, replicative senescence, phagocytosis, or apoptosis, for further cell biological research approaches.

In dieser Dissertation werden die Resultate eines optimal gestalteten Energieeinsatzes bei der Lebensmittelverarbeitung auf die Lebensmittelqualität und die entsprechenden Auswirkungen auf die Ernährungssicherheit im ländlichen Mosambik untersucht. Sie ergänzt die aktuelle wissenschaftliche Literatur, da sie 1) ein ganzheitliches Verständnis von Ernährungssicherung und der zugrundeliegenden Treiber vermittelt. Darüber hinaus trägt sie 2) zum Verständnis der technischen Leistungsfähigkeit optimal konzipierter Lebensmittelverarbeitungs- und -Lebensmittelzubereitungstechnologien bei. Diese Dissertation liefert zudem 3) Erkenntnisse über die Verbraucherakzeptanz, der mit diesen Technologien verarbeiteten und zubereiteten Lebensmittel. Weiterhin stellt sie 4) die Auswirkungen von neu eingeführten Lebensmittelverarbeitungstechnologie auf die Ernährungssicherheit dar. Schließlich wird 5) die Bedeutung des „Verbreitungsansatzes“ für den Erfolg der Einführung von „Clean Cooking“ Technologien diskutiert. Um all diesen Aspekten gerecht zu werden besteht diese Dissertation aus acht Kapiteln und die Ergebnisse werden in fünf einzelnen Unterkapitel vorgestellt. Die generellen Ergebnisse dieser Dissertation sind, dass erstens die in dieser Arbeit dargestellten Technologien nachhaltig und kosteneffizient genug sind um, zumindest temporär, die vorherrschenden traditionellen Methoden der Lebensmittelverarbeitung und Lebensmittelzubereitung zu ersetzen. Zweitens ist der Zugang zu Energie durch passive Solartrockner eine wichtige Komponente im Kampf gegen den Hunger und generelle Ernährungsunsicherheit. Drittens sollten Regierungen und relevante Akteure in den Kampf gegen Hunger und Energieunsicherheit die lokalen Kontexte in ihre Planungen einbeziehen und die entsprechenden und angemessenen Bildungs- oder Informationsansätze wählen. / This dissertation explores the effects of optimally designed processing energy usage on food quality and the respective impacts on FNS in rural Mozambique. It adds to the current literature, as it provides 1) a holistic understanding of the nature of FNS and its underlying drives. Furthermore, 2) it adds to the understanding of the technical performance of optimally designed food processing and preparation technologies. 3) The dissertation provides insights concerning users’ acceptability of the food processed and prepared through these technologies. 4) The effects of the newly introduced food processing technology on FNS are presented. Last – but not least – 5) it discusses the importance of the dissemination approach for the success of clean cooking adoption. This PhD dissertation is comprised of 8 chapters and the results are presented in five individual subchapters. The general conclusions of this thesis are that 1) the improved technologies presented in this study are sustainable and cost-effective means to substitute, at least temporarily, the prevailing traditional methods of food processing and food preparation; 2) energy provision through the use of passive solar drying is an essential component in the fight against food and nutrition insecurity and 3) governments and relevant stakeholders involved in energy and food security programs are advised to consider the local context to identify the most adequate training or information delivery technique.